What is the recommended dose of Dapagliflozin (Forxiga) for a patient with Heart Failure with Reduced Ejection Fraction (HFrEF), Diabetes Mellitus (DM), and Chronic Kidney Disease (CKD)?

Dapagliflozin Dosing in HFrEF with Diabetes and CKD

The recommended dose of dapagliflozin for a patient with HFrEF, diabetes mellitus, and CKD is 10 mg orally once daily, provided the eGFR is ≥25 mL/min/1.73 m² 1.

Dosing Algorithm Based on eGFR

For cardiovascular and renal protection (HFrEF and CKD indications):

• eGFR ≥25 mL/min/1.73 m²: Initiate dapagliflozin 10 mg once daily 1
• eGFR <25 mL/min/1.73 m²: Do not initiate dapagliflozin 1
• If eGFR falls below 25 mL/min/1.73 m² while on treatment: Continue dapagliflozin 10 mg daily until dialysis is required 1

For glycemic control specifically:

• eGFR ≥45 mL/min/1.73 m²: Start at 5 mg once daily, may increase to 10 mg if additional glycemic control needed 1
• eGFR <45 mL/min/1.73 m²: Do not use for glycemic control (ineffective due to mechanism of action) 1

Critical Point: Single Fixed Dose for Multiple Indications

In your patient with HFrEF, diabetes, and CKD, use 10 mg once daily as a single dose that addresses all three conditions simultaneously 2. This fixed dose provides cardiovascular protection (reducing CV death and HF hospitalization by 26% in DAPA-HF), renal protection (reducing kidney failure risk by 44% in DAPA-CKD), and some glycemic benefit if eGFR permits 3, 4, 5.

Evidence Supporting This Dosing Strategy

The 2021 ACC Expert Consensus Decision Pathway emphasizes that dapagliflozin 10 mg daily reduces cardiovascular death or worsening heart failure by 26% (HR 0.74,95% CI 0.65-0.85) in HFrEF patients regardless of diabetes status 3. The DAPA-CKD trial demonstrated that this same 10 mg dose reduces the composite renal outcome by 44% (HR 0.56,95% CI 0.45-0.68) in CKD patients with eGFR 25-75 mL/min/1.73 m² 2, 5.

The benefits are consistent across the spectrum of kidney function down to eGFR 25 mL/min/1.73 m², with no dose adjustment required 3. The DAPA-HF trial excluded patients with eGFR <30 mL/min/1.73 m², but FDA approval extends to eGFR ≥25 mL/min/1.73 m² based on the totality of evidence 3, 1.

Pre-Initiation Assessment

Before starting dapagliflozin:

• Assess renal function (eGFR and creatinine) to confirm eGFR ≥25 mL/min/1.73 m² 1
• Evaluate volume status and correct any volume depletion before initiation 1
• Check blood pressure to ensure patient can tolerate mild diuretic effect 2

Expected Initial eGFR Changes

An initial eGFR decline of 3-5 mL/min/1.73 m² within the first 1-4 weeks is expected and reversible 2. This hemodynamic dip does not predict worse outcomes; in fact, patients experiencing this initial decline had better long-term renal outcomes with slower subsequent eGFR decline (-1.58 vs -2.44 mL/min/1.73 m²/year) 2, 6.

• Recheck eGFR and creatinine 1-2 weeks after initiation 2
• If eGFR decreases >30% from baseline AND signs of hypovolemia present: Reduce diuretic doses first before considering dapagliflozin adjustment 2
• Do not discontinue dapagliflozin for an initial eGFR dip alone 2, 6

Monitoring and Safety Considerations

Withhold dapagliflozin at least 3 days before major surgery or procedures requiring prolonged fasting to prevent postoperative ketoacidosis 2, 1.

During acute illness (fever, vomiting, diarrhea, reduced oral intake):

• Temporarily discontinue dapagliflozin 2
• Monitor for euglycemic diabetic ketoacidosis (DKA), which can occur even with normal blood glucose 2
• Check blood or urine ketones if patient develops malaise, nausea, or vomiting 2
• Resume only after recovery and normal oral intake is re-established 2

Monitor for adverse effects:

• Genital mycotic infections and urinary tract infections (more common with SGLT2 inhibitors) 2, 1
• Volume depletion (especially in elderly or those on diuretics) 2, 1
• Euglycemic DKA (rare but serious, particularly in insulin-treated patients) 2, 1

Common Pitfall to Avoid

Do not reduce or discontinue dapagliflozin solely because eGFR is <45 mL/min/1.73 m² 3, 2. While the glucose-lowering effect diminishes at lower eGFR levels, the cardiovascular and renal protective benefits are preserved down to eGFR 25 mL/min/1.73 m² 3, 2. The 10 mg dose remains appropriate for HFrEF and CKD indications even when glycemic efficacy is lost 1.

Timing of Therapy Initiation

The ACC recommends achieving optimal guideline-directed medical therapy (GDMT) within 3-6 months of HF diagnosis, with medication adjustments every 2 weeks 3. Dapagliflozin should be initiated early as part of foundational HFrEF therapy alongside ACE inhibitors/ARNIs, beta-blockers, and mineralocorticoid receptor antagonists 3.